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Fatty Fish consumption Reduces lipophilic index in erythrocyte membranes and serum phospholipids
Abstract
Background and aims:
Lipophilic index (LI) has been introduced to assess the overall fatty acid lipophilicity and as a simple estimate of membrane fluidity. However, little is known on effect of diet on LI. We tested if Camelina sativa oil (CSO) high in ALA, fatty fish (FF) or lean fish (LF) affect LI as compared to control diet and, secondarily, if the LI is associated with HDL lipids and functionality and LDL lipidome.
Methods and results:
We used data from two randomized clinical trials. The AlfaFish intervention lasted 12 weeks and 79 subjects with impaired glucose tolerance were randomized to FF, LF, CSO or control group. In the Fish trial, 33 subjects with myocardial infarction or unstable ischemic heart attack were randomized to FF, LF or control group for 8 weeks. LI was calculated from erythrocyte membrane fatty acids in AlfaFish and from serum phospholipids in Fish trial. HDL lipids were measured using high-throughput proton nuclear magnetic resonance spectroscopy. There was a significant decrease in LI in the FF group in the AlfaFish (fold change 0.98 ± 0.03) and in the Fish trial (0.95 ± 0.04) and the decrease differed from that of control group in both trials and from CSO group in the AlfaFish study. There were no significant changes in LI in LF or CSO groups. The mean diameter of HDL particles and concentration of large HDL particles were inversely associated with LI.
Conclusion:
FF consumption decreased LI indicating better membrane fluidity in subjects with impaired glucose tolerance or coronary heart disease.
... We showed that in T2D patients with ASCVD, a higher serum phospholipid LI is associated with increased serum concentrations of TCh and LDL-Ch. Previous population-based studies have shown a link between LI and abnormal lipid profile, including higher levels of LDL-Ch and TG [15,37,38]. However, the relationship between serum phospholipid LI and lipid parameters has not been evaluated in patients with T2D, who usually have complex lipoprotein abnormalities known as atherogenic dyslipidemia and characterized by elevated fasting and postprandial TG levels, low HDL-Ch, and increased small dense LDL particles. ...
... Individual FAs, particularly n-3 and n-6 PUFAs, had a differential effect on LI values which is consistent with the results of previous studies [14,19,28]. As a higher content of n-3 PUFAs -eicosapentaenoic (EPA) and docosahexaenoic (DHA) -has a beneficial effect on the fluidity of biological membranes and on reducing the value of LI, and consumption of marine fish rich in these FAs significantly reduces LI of serum phospholipids and erythrocyte membranes [37], it can be supposed that the association observed in our study between serum phospholipid LI and vascular inflammation is related to the anti-inflammatory properties of these n-3 PUFAs. Moreover, arachidonic acid, a member of the n-6 PUFA family whose anti-inflammatory properties are well known [43,44], has a similar effect on LI. ...
Background
Little is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD.
Methods
We studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed.
Results
Patients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA2 (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA2 were predictors of LI > 16.9 °C in adjusted models.
Conclusions
In well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses.
... Finally, a recent study showed that fish consumption leads to a reduction in the lipophilic index in the erythrocyte membrane that is inversely correlated with HDL diameter [79]. Thus, HDL particles could indirectly affect EMF by reducing oxidative stress after an omega-3 trigger [80]. ...
Omega-3 fatty acids reduce triglycerides and have several positive effects on different organs and systems. They are also found in the plasma membrane in variable amounts in relation to genetics and diet. However, it is still unclear whether omega-3 supplementation can reduce the occurrence of major cardiovascular events (MACEs). Two trials, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), with highly purified EPA, and STRENGTH (Effect of High-Dose Omega-3 Fatty Acids vs. Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk), with a combination of EPA and DHA, have produced different outcomes, triggering a scientific debate on possible explanations for the discrepancies. Furthermore, doubts have arisen as to the anti-inflammatory and anti-aggregating activity of these compounds. Recent studies have, however, highlighted interesting effects of EPA and DHA on erythrocyte membrane fluidity (EMF). EMF is governed by a complex and dynamic biochemical framework, with fatty acids playing a central role. Furthermore, it can be easily measured in erythrocytes from a blood sample using fluorescent probes. Recent research has also shown that EMF could act as a possible cardiovascular risk factor biomarker. This review aims to synthetize the latest evidence on erythrocyte membrane fluidity, exploring its potential role as a biomarker of residual cardiovascular risk and discussing its clinical relevance. Further, we aim to dissect the possible biological mechanisms that link omega-3 modifiable membrane fluidity to cardiovascular health.
Omega-3 (ω-3) fatty acids have been extensively studied for primary and secondary prevention of cardiovascular health, but their ability to modulate HDL functionality remains unclear. The purpose of this study was to investigate the role of ω-3, rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA), on HDL functionality. For that, 147 individuals with high cardiovascular risk were randomized in ω-3 (1 g of fish oil each - 370 mg of EPA and 230 mg of DHA, 3 times per day total EPA+DHA = 1,800 mg) or ω-6 groups (1 g of sunflower oil each - 760 mg of linoleic acid, 3 times per day; total linoleic acid = 2,280 mg). Fasting blood samples were collected at baseline time and after 8 weeks of follow-up and, and the lipid profile and glucose metabolism were evaluated from plasma. From HDL, the fatty acid profile, apolipoproteins (Apo AI, CII and CIII), paraoxonase-1 (PON1), cholesteryl ester transfer protein (CETP), subfractions and antioxidant activity were investigated. Omega-3 improved large HDL (HDL = 28.7%) and reduced small HDL (HDL10 = −10.6%) and the non-esterified fatty acids in HDL (NEFAs-HDL) level (−16.2%). A significant reduction in CETP activity was observed in the ω-3group (Δ ω-6 = 3.60 pmol/ul/h and Δ ω-3 = −1.99 pmol/ul/h; p = 0.044). The antioxidant capacity estimated by Lag time analysis did not change after the ω-3intervention. Changes in PON1 and Apo AI were inversely associated with increased incorporation of EPA (AOR = 0.446; IC = 0.200–0.994) and DHA (AOR = 0.351; IC = 0.150–0.821) in HDL, respectively. Cardioprotective profile obtained by pooled fatty acids analysis was related to a decrease in Apo CIII (r = −0.638; p = 0.002) and CETP (r = −0.341; p = 0.012) and an increase in Apo CII (r = 0.448; p = 0.042) and PON1 (r = 0.388; p = 0.003). In conclusion, omega-3 was effective in the reduction of cardiovascular risk associated with HDL functionality by size improvement and changes in its lipid, antioxidant and enzyme composition.
High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.
Objective
We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity.
Approach and Results
The participants (36 subjects; age, 48±10 years; body mass index, 30.9±6.2 kg/m ² ) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group.
Conclusions
The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans.
REGISTRATION
URL: http://www.clinicaltrials.gov ; Unique identifier NCT02133144.
Reverse cholesterol transport (RCT) is a physiological mechanism protecting cells from an excessive accumulation of cholesterol. When this process begins in vascular macrophages, it acquires antiatherogenic properties, as has been widely demonstrated in animal models. Dietary lipids, despite representing a fundamental source of energy and exerting multiple biological functions, may induce detrimental effects on cardiovascular health. In the present review we summarize the current knowledge on the mechanisms of action of the most relevant classes of dietary lipids, such as fatty acids, sterols and liposoluble vitamins, with effects on different steps of RCT. We also provide a critical analysis of data obtained from experimental models which can serve as a valuable tool to clarify the effects of dietary lipids on cardiovascular disease.
High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.
Background
Dietary fatty acids are important dietary determinants of metabolic disorders in human. However, it is important to develop an index that considers not only the amount of dietary fatty acids but also the structure, fluidity and melting point of them. In the current study we investigated the association between a novel dietary lipophilic index (LI) with metabolic profile and dyslipidemia in a community based study in Tabriz-Iran.
Methods
Dietary data were collected using a validated, 79-food item, semi-quantitative food frequency questionnaire, and dietary LI was calculated. Anthropometric variables were measured and metabolic profile including blood sugar, serum lipids and liver enzymes were assessed. Metabolic syndrome was defined according to the adult treatment panel (ATP) III criteria.
Results
The mean age of the participants was 42.53 ± 12.03 years and most of the participants were women. Mean of dietary LI was 34.99 ± 6.91. Higher dietary LI was associated with higher body mass index (BMI) (β = 0.17, P < 0.04), waist circumference (β = 0.18, P < 0.01) and systolic blood pressure (β = 0.27, P < 0.01). Also LI was increased with increasing waist circumference (0.001), low density lipoprotein cholesterol (LDL-C) (0.001), and negatively associated with high density lipoprotein cholesterol (HDL-C) (0.001).
Conclusion
The novel dietary LI was considered as a useful tool in prediction of cardio-metabolic risk factors including general and central obesity, dyslipidemia and metabolic syndrome in a population-based study in Iran. Further researches in other disease and populations could highlight the application of this index in clinical settings.
A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e. annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labelled compounds in metabolic labelling experiments or as internal standards.
This update on lipid classification, nomenclature and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.
Background:
South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality.
Objective:
We hypothesized that LDL of South Asians is more prone to aggregate, which may be explained by differences in their LDL lipid composition.
Methods:
In this cross-sectional hypothesis-generating study, LDL was isolated from plasma of healthy South Asians (n = 12) and age- and BMI-matched white Caucasians (n = 12), and its aggregation susceptibility and lipid composition were analyzed.
Results:
LDL from South Asians was markedly more prone to aggregate compared with white Caucasians. Among all measured lipids, sphingomyelin 24:0 and triacylglycerol 56:8 showed the highest positive correlation with LDL aggregation. In addition, LDL from South Asians was enriched in arachidonic acid containing phosphatidylcholine 38:4 and had less phosphatidylcholines and cholesteryl esters containing monounsaturated fatty acids. Interestingly, body fat percentage, which was higher in South Asians (+26%), positively correlated with LDL aggregation and highly positively correlated with triacylglycerol 56:8, sphingomyelin 24:0, and total sphingomyelin.
Conclusions:
LDL aggregation susceptibility is higher in healthy young South Asians compared with white Caucasians. This may be partly explained by the higher body fat percentage of South Asians, leading to sphingomyelin enrichment of LDL. We anticipate that the presence of sphingomyelin-rich, aggregation-prone LDL particles in young South Asians may increase LDL accumulation in the arterial wall and thereby contribute to their increased risk of developing ASCVD later in life.
Background and aim:
Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis.
Methods and results:
Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect β = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden.
Conclusion:
Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
Diet may influence the risk of ischemic stroke by several mechanisms. A potential and hitherto unknown mechanism may relate to an effect on the lipophilic index, which is a new and convenient indicator of membrane fluidity. This study investigated the association between the adipose tissue lipophilic index and ischemic stroke and its subtypes. A case-cohort study was conducted based on the Danish cohort study Diet, Cancer, and Health, which includes 57,053 subjects aged 50–64 years at enrolment. A subcohort (n = 3500) was randomly drawn from the whole cohort. All ischemic stroke cases were validated and categorized into subtypes. The lipophilic index was calculated based on fatty acid profiles in adipose tissue. Subjects were divided into quintiles and a weighted Cox proportional hazards regression model was used to calculate hazard ratios. After appropriate exclusions, a subcohort of 3194 subjects and 1752 cases of ischemic stroke were included. When comparing the fifth quintile of the lipophilic index with the first quintile, the hazard ratio for ischemic stroke was 0.92 (95% confidence interval 0.75, 1.13) and the trend across quintiles was not statistically significant (p = 0.1727). In conclusion, no association was found between the lipophilic index and ischemic stroke or its subtypes.
Aims:
Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization.
Methods and results:
We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture.
Conclusion:
Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.
Background
Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear.
Objective
The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity.
Methods
The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m²): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid–canola oil, DHA-enriched high oleic acid–canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure.
Results
The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = −0.25, P = 0.01, r = −0.33, P = 0.02, respectively).
Conclusion
Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.
Scope:
Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion.
Methods and results:
Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity.
Conclusions:
HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions. This article is protected by copyright. All rights reserved.
Previous studies indicate that reduced concentrations of circulating high-density lipoprotein (HDL) particles can be superior to HDL-cholesterol (HDL-C) levels as a predictor of cardiovascular disease. Measurements of HDL particle numbers, therefore, bear a potential for the improved assessment of cardiovascular risk. Furthermore, such measurement can be relevant for the evaluation of novel therapeutic approaches targeting HDL. Modern in-depth analyses of HDL particle profile may further improve evaluation of cardiovascular risk. Although clinical relevance of circulating concentrations of HDL subpopulations to cardiovascular disease remains controversial, the negative relationship between the number of large HDL particles and cardiovascular disease suggests that assessment of HDL particle profile can be clinically useful. Reduced mean HDL size is equally associated with cardiovascular disease in large-scale clinical studies. Since HDL-C is primarily carried in the circulation by large, lipid-rich HDL particles, the inverse relationship between HDL size and cardiovascular risk can be secondary to those established for plasma levels of HDL particles, HDL-C, and large HDL. The epidemiological data thereby suggest that HDL particle number may represent a more relevant therapeutic target as compared to HDL-C.
Erythrocyte membrane fatty acid (EMFA) composition is used in the validation of food frequency questionnaires (FFQ) and the evaluation of dietary fat quality. In this cross-sectional study we aimed to investigate associations of diet with EMFA. Altogether, 1,033 randomly selected Finnish men, aged from 47 to 75 years filled in a FFQ and their EMFA composition was analyzed. Marine polyunsaturated fatty acid (PUFA) intake correlated positively with erythrocyte eicosapentaenoic and docosahexaenoic acids (r
s = 0.415 and r
s = 0.340, respectively, P < 0.001) and inversely with all n-6 PUFA analyzed (P < 0.001). PUFA intake from spreads and cooking fats correlated positively with alpha-linolenic (ALA), linoleic (LNA) and nervonic acids (r
s = 0.229, r
s = 0.160 and r
s = 0.143, respectively, P < 0.001). Milk fat intake was associated with myristic and behenic acids (r
s = 0.186 and r
s = 0.132, respectively P < 0.001). Butter users had lower ALA and LNA proportions (mol%) than non-users (0.16 ± 0.04 vs. 0.19 ± 0.05, P < 0.001 and 7.77 ± 1.02 vs. 8.12 ± 1.11, P = 0.001). Higher PUFA intake from meat was related to decreased long-chain n-3 (P < 0.001) and increased n-6 PUFA (P < 0.001) proportions. In conclusion, EMFA composition reflects particularly well the intakes of n-3 PUFA, whereas other associations remained lower. Yet, all main sources of dietary fat were related with EMFA. The dietary effect on the nervonic acid proportion was confirmed.
The lipophilic index (LI), a mean measure of fatty acid melting points, has been proposed to capture overall fatty acid profile and may play an important role in the etiology of coronary heart disease. We aimed to determine the association between LI in diet and in adipose tissue and metabolic risk factors for myocardial infarction (MI) and risk of MI. We used a population-based, matched case-control study of nonfatal first acute MI conducted in Costa Rica between 1994 and 2004, with 1,627 case-control pairs. The LI is defined as the mean of the melting points of specific fatty acids in diet or adipose tissue. LIs in diet and adipose tissue were significantly associated with higher plasma triglyceride concentrations, low-density lipoprotein cholesterol concentrations, and low-density:high-density lipoprotein cholesterol ratio. Comparing extreme quintiles for the LI in diet or adipose tissue, the odds ratios for MI were 1.57 (95% confidence interval: 1.22, 2.02; P for trend < 0.001) for dietary LI and 1.30 (95% confidence interval: 1.00, 1.69; P for trend = 0.02) for adipose tissue LI in the multivariable models. We hypothesize that a higher LI in diet and in adipose tissue represents decreased fatty acid fluidity and could play an important role in the etiology of coronary heart disease.
Few epidemiological studies have examined the association between an overall fatty acid (FA) profile and CHD risk. The aim of the present study was to examine a novel index that summarises individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case-control study, FA in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers and adiponectin. After multivariate adjustment for age, smoking, BMI and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1·61 (95 % CI 1·03, 2·53; P for trend = 0·04) comparing extreme quintiles. This association was attenuated to 1·21 (95 % CI 0·48, 3·09; P for trend = 0·77) after adjusting for plasma levels of total trans-FA, long-chain n-3 FA and polyunsaturated:saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. The present data indicate that a novel LI is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men; its usefulness as a complement of individual FA in assessing disease risk needs to be elucidated in future studies.
Comprehensive characterization of human tissues promises novel insights into the biological architecture of human diseases and traits. We assessed metabonomic, transcriptomic, and genomic variation for a large population-based cohort from the capital region of Finland. Network analyses identified a set of highly correlated genes, the lipid–leukocyte (LL) module, as having a prominent role in over 80 serum metabolites (of 134 measures quantified), including lipoprotein subclasses, lipids, and amino acids. Concurrent association with immune response markers suggested the LL module as a possible link between inflammation, metabolism, and adiposity. Further, genomic variation was used to generate a directed network and infer LL module's largely reactive nature to metabolites. Finally, gene co-expression in circulating leukocytes was shown to be dependent on serum metabolite concentrations, providing evidence for the hypothesis that the coherence of molecular networks themselves is conditional on environmental factors. These findings show the importance and opportunity of systematic molecular investigation of human population samples. To facilitate and encourage this investigation, the metabonomic, transcriptomic, and genomic data used in this study have been made available as a resource for the research community.
Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomized, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo. Markers of cardiovascular risk were assessed before and after treatment. In the DHA-supplemented group, the decrease in mean VLDL particle size (P ≤ 0.001) and increases in mean LDL (P ≤ 0.001) and HDL (P ≤ 0.001) particle sizes were significantly greater than changes in the placebo group. DHA supplementation also increased the concentrations of large LDL (P ≤ 0.001) and large HDL particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009) and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P = 0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than placebo (P = 0.021), but no other significant changes were observed in glucose metabolism, insulin sensitivity, blood pressure, or markers of inflammation with DHA. In summary, DHA supplementation resulted in potentially beneficial changes in some markers of cardiometabolic risk, whereas other markers were unchanged.
A rapid and simple method for separation of serum lipid classes for fatty acid analysis with a single aminopropyl solid phase glass column is described. The recoveries of cholesteryl esters, triglycerides, free fatty acids, and phospholipids were all at least 98%. Coefficients of variation less than 10% were obtained for absolute and relative amounts of most individual fatty acids analyzed after separation of serum lipid classes. This method provides an efficient and convenient tool to follow fatty acid patterns in serum lipid fractions.
The purpose of this study was to test the hypothesis that lipid fluidity regulates lecithin:cholesterol acyltransferase (LCAT) activity. Phosphatidylcholine (PC) species were synthesized that varied in fluidity by changing the number, type (cis vs. trans), or position of the double bonds in 18 or 20 carbon sn-2 fatty acyl chains and recombined with [³H]cholesterol and apolipoprotein A-I to form recombinant high density lipoprotein (rHDL) substrate particles. The activity of purified human plasma LCAT decreased with PC sn-2 fatty acyl chains containing trans versus cis double bonds and as double bonds were moved towards the methyl terminus of the sn-2 fatty acyl chain. The decrease in LCAT activity was significantly correlated with a decrease in rHDL fluidity (measured by diphenylhexatriene fluorescence polarization) for PC species containing 18 carbon (r² = 0.61, n = 18) and 20 carbon (r² = 0.93, n = 5) sn-2 fatty acyl chains. rHDL were also made containing 10% of the 18 carbon sn-2 fatty acyl chain PC species and 90% of an inert PC ether matrix (sn-1 18:1, sn-2 16:0 PC ether) to normalize rHDL fluidity. Even though fluidity was similar among the PC ether-containing rHDL, the order of PC reactivity with LCAT was significantly correlated (r² = 0.71) with that of 100% PC rHDL containing the same 18 carbon sn-2 fatty acyl chain species, suggesting that PC structure in the active site of LCAT determines reactivity in the absence of measurable differences in bilayer fluidity. We conclude that PC fluidity and structure are major regulators of LCAT activity when fatty acyl chain length is constant.
—Parks, J. S., K. W. Huggins, A. K. Gebre, and E. R. Burleson. Phosphatidylcholine fluidity and structure affect lecithin:cholesterol acyltransferase activity. J. Lipid Res. 2000. 41: 546–553.
To measure effects of fish oil supplements on lipoprotein subclasses by nuclear magnetic resonance (NMR) in subjects with type II diabetes and relate them to insulin sensitivity.
Two-armed, parallel, placebo-controlled, randomized.
Normotriglyceridemic subjects with type II diabetes without insulin treatment were given either fish oil (n=12, median intake 5.9 g/day total n-3 fatty acids (FA) (1.8 g 20:5n-3, 3.0 g 22:6n-3)) or corn oil (n=14, 8.5 g/day 18:2n-6 FA).
Size and concentration of lipoproteins subclasses were measured by NMR, insulin sensitivity by hyperinsulinemic, isoglycemic clamps.
After 9 weeks, there were differences between those treated with fish and corn oil with respect to very low-density lipoprotein (VLDL) size (median -15 vs +0.6%, P=0.001), particle concentrations of large VLDL (-99 vs -4.1%, P=0.041) and small high-density lipoprotein (HDL) (-12 vs +10%, P=0.051). Compared with corn oil fish oil tended to increase HDL size and small low-density lipoprotein (LDL) concentration (P=0.063 and 0.068, respectively, for differences between groups). There was no effect on oxidized LDL. Insulin sensitivity (glucose utilization) decreased in the fish oil group compared with the corn oil group (P=0.049). The decrease in insulin sensitivity did not correlate with the effects on lipoprotein subclasses.
A high intake of n-3 FA exerts effects on several lipoprotein subclasses without obvious influence from changes in insulin sensitivity.
There is much interest in the significance of apolipoproteins and proteins that are noncovalently associated with lipoproteins. It is possible that the high ionic strength used for isolation of lipoproteins with KBr and NaI could alter the pattern of associated exchangeable proteins. Here we describe lipoprotein classes fractionation from up to 0.5 ml of serum or plasma with buffers of physiological ionic strength and pH prepared with deuterium oxide (D(2)O) and sucrose. An advantage of the D(2)O/sucrose procedure was that the lipoproteins could be directly analyzed by the techniques described without need for desalting. We compared the isolated lipoproteins with those obtained using ultracentrifugation in KBr from the same plasma pool. Electrophoretic homogeneity of the lipoproteins was very similar using the two methods, as well as their lipid composition evaluated by HPLC. Two-dimensional electrophoresis and surface-enhanced laser adsorption/ionization time-of-flight mass spectrometry indicated that the patterns of exchangeable proteins of VLDL isolated using with the two procedures were very similar. However, significant differences were found in the profiles of LDL and HDL, indicating that the D(2)O/sucrose method allowed a more complete characterization of its exchangeable apolipoproteins and proteins.
Background
There is little knowledge on the effects of alpha-linolenic acid (ALA) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) on the LDL lipidome and aggregation of LDL particles.
Objective
We examined if consumption of Camelina sativa oil (CSO) as a source of ALA, fatty fish (FF) as a source of n-3 LCPUFA and lean fish (LF) as a source of fish protein affect the lipidome of LDL as compared to a control diet.
Methods
Participants with impaired glucose tolerance (39 women and 40 men) were randomized to 4 study groups (CSO providing 10 g/d ALA, FF and LF [both 4 fish meals/wk] and control limiting their fish and ALA intake) in a 12-week, parallel trial. Diets were instructed and dietary fats were provided to the participants. The lipidome of LDL particles isolated from samples collected at baseline and after intervention was analyzed with electrospray ionization-tandem mass spectrometry.
Results
In the CSO group, the relative concentrations of saturated and monounsaturated cholesteryl ester species in LDL decreased and the species with ALA increased. In the FF group, LDL phosphatidylcholine (PC) species containing n-3 LCPUFA increased. There was a significant positive correlation between the change in total sphingomyelin and change in LDL aggregation, while total PC and triunsaturated PC species were inversely associated with LDL aggregation when all the study participants were included in the analysis.
Conclusion
Dietary intake of CSO and FF modifies the LDL lipidome to contain more polyunsaturated and less saturated lipid species. The LDL surface lipids are associated with LDL aggregation.
Background and aims:
Omega-3 fatty acids are known to have several cardioprotective effects. Our aim was to investigate the effects of intakes of fish and Camelina sativa oil (CSO), rich in alpha-linolenic acid, on the atherogenic and anti-atherogenic functions of LDL and HDL particles.
Methods:
Altogether, 88 volunteers with impaired glucose metabolism were randomly assigned to CSO (10 g of alpha-linolenic acid/day), fatty fish (4 fish meals/week), lean fish (4 fish meals/week) or control group for 12 weeks. 79 subjects completed the study. The binding of lipoproteins to aortic proteoglycans, LDL aggregation and activation of endothelial cells by LDL and cholesterol efflux capacity of HDL were determined in vitro.
Results:
Intake of CSO decreased the binding of lipoproteins to aortic proteoglycans in a non-normalized model (p = 0.006). After normalizing with serum concentrations of non-HDL cholesterol, apolipoprotein B (apoB) or LDL cholesterol, which decreased in the CSO group, the change was no longer statistically significant. In the fish groups, there were no changes in the binding of lipoproteins to proteoglycans. Regarding other lipoprotein functions, there were no changes in any of the groups.
Conclusions:
Intake of CSO decreases the binding of lipoproteins to aortic proteoglycans by decreasing serum LDL cholesterol concentration, which suggests that the level of apoB-containing lipoproteins in the circulation is the main driver of lipoprotein retention within the arterial wall. Intake of fish or CSO has no effects on other lipoprotein functions.
Scope
Intake of long‐chain n‐3 PUFAs affects the lipoprotein subclass profile, whereas the effect of shorter chain n‐3 PUFAs remains unclear. We investigated the effect of fish and camelina sativa oil (CSO) intakes on lipoprotein subclasses.
Methods and results
Altogether 79 volunteers with impaired glucose metabolism were randomly assigned to CSO, fatty fish (FF), lean fish (LF) or control group for 12 weeks. Nuclear magnetic resonance spectroscopy was used to determine lipoprotein subclasses and their lipid components. The average HDL particle size increased in the FF group (overall p = 0.032) as compared with the control group. Serum concentrations of cholesterol in HDL and HDL2 (overall p = 0.024 and p = 0.021, respectively) and total lipids and phospholipids in large HDL particles (overall p = 0.012 and p = 0.019, respectively) increased in the FF group, differing significantly from the LF group. The concentration of intermediate‐density lipoprotein (IDL) particles decreased in the CSO group (overall p = 0.033) as compared with the LF group.
Conclusion
Our study suggests that FF intake causes a shift towards larger HDL particles and increases the concentration of lipid components in HDL, which may be associated with the antiatherogenic properties of HDL. Furthermore, CSO intake decreases IDL particle concentration. These changes may favorably affect cardiovascular risk.
This article is protected by copyright. All rights reserved
Scope:
The aim of the study was to examine whether lean fish (LF), fatty fish (FF) and camelina sativa oil (CSO), a plant-based source of alpha-linolenic acid (ALA), differ in their metabolic effects in subjects with impaired glucose metabolism.
Methods and results:
Altogether 79 volunteers with impaired fasting glucose, BMI 25-36 kg/m2 , age 43-72 years, participated in a 12-week randomized controlled trial with four parallel groups, i.e. the FF (4 fish meals/week), LF (4 fish meals/week), CSO (10 g/day ALA) and control (limited intakes of fish and source of ALA) groups. The proportions of EPA and DHA increased in plasma lipids in the FF group, and the proportion of ALA increased in the CSO group (P < 0.0001 for all). In the CSO group total and LDL-cholesterol (C) concentrations decreased compared with the FF and LF groups, LDL-C/HDL-C and ApoB/ApoA-I ratios decreased compared with the LF group. There were no significant changes in glucose metabolism or markers of low-grade inflammation.
Conclusions:
A diet enriched in CSO improves serum lipid profile as compared with a diet enriched in FF or LF in subjects with impaired fasting glucose, with no differences in glucose metabolism or concentrations of inflammatory markers. This article is protected by copyright. All rights reserved.
Background and aims
The fluidity of dietary fatty acids consumed has been suggested to inversely affect coronary heart disease (CHD) risk. Lipophilic index (LI) represents overall fluidity of the dietary fatty acid profile. Lipophilic load (LL) represents a combination of overall fluidity and absolute intake of dietary fatty acids. We investigated the relations of dietary LI and LL with risk of CHD and ischemic stroke (iStroke).
Methods and results
We used data from the prospective EPIC-NL study, including 36,520 participants aged 20-70 years. LI and LL were calculated using dietary intake data estimated with a validated FFQ. Incident CHD (n=2348) and iStroke (n=479) cases were obtained through linkage to national registers during 15 years follow-up. LI and LL were not associated with CHD risk (HRshighest-versus-lowest-quartiles : 0.93 [95%CI: 0.83, 1.04], and 0.92 [95%CI: 0.79, 1.07], respectively), and neither with iStroke risk (HRs 1.15 (95%CI: 0.89, 1.48), and 0.98 (95%CI: 0.70, 1.38), respectively). Original fatty acid classes (SFA, MUFA and PUFA), and LI and LL stratified by these fatty acid classes, were overall not related to CHD and ischemic stroke either.
Conclusions
In this Dutch population, neither the overall fluidity of the dietary fatty acid profile (LI), nor the combined fluidity and amount of fatty acids consumed (LL) were related to CHD or iStroke risk. Dietary LI and LL may have limited added value above original fatty acid classes and food sources in establishing the relation of fatty acid consumption with CVD.
The present work aimed to evaluate and compare, for the first time, the effects of extra virgin olive oil (EVOO) and hybrid palm oil (HPO) supplementation on fatty acid profile and phospholipid (PL) molecular species composition of human erythrocyte membranes. Results supported the effectiveness of both HPO and EVOO supplementation (3-month, 25mL/day) in decreasing the lipophilic index of erythrocytes with no significant differences between HPO and EVOO groups at month 3. On the other hand, the novel and rapid UPLC/MS/MS method used for PL analysis reveals an increase in phosphatidylcholine and phosphatidylethanolamine species esterified with polyunsaturated fatty acids. The present work demonstrated the ability of both EVOO and HPO to increase the degree of unsaturation of erythrocyte membrane lipids with an improvement in the membrane fluidity that could be associated with a lower risk to develop cardiovascular diseases.
Metabolomics is becoming common in epidemiology due to recent developments in quantitative profiling technologies and appealing results from their applications for understanding health and disease. Our team has developed an automated high-throughput serum NMR metabolomics platform that provides quantitative molecular data on 14 lipoprotein subclasses, their lipid concentrations and composition, apolipoprotein A-I and B, multiple cholesterol and triglyceride measures, albumin, various fatty acids as well as on numerous low-molecular-weight metabolites, including amino acids, glycolysis related measures and ketone bodies. The molar concentrations of these measures are obtained from a single serum sample with costs comparable to standard lipid measurements. We have analyzed almost 250 000 samples from around 100 epidemiological cohorts and biobanks and the new international set-up of multiple platforms will allow an annual throughput of more than 250 000 samples. The molecular data have been used to study type 1 and type 2 diabetes etiology as well as to characterize the molecular reflections of the metabolic syndrome, long-term physical activity, diet and lipoprotein metabolism. The results have revealed new biomarkers for early atherosclerosis, type 2 diabetes, diabetic nephropathy, cardiovascular disease and all-cause mortality. We have also combined genomics and metabolomics in diverse studies. We envision that quantitative high-throughput NMR metabolomics will be incorporated as a routine in large biobanks; this would make perfect sense both from the biological research and cost point of view - the standard output of over 200 molecular measures would vastly extend the relevance of the sample collections and make many separate clinical chemistry assays redundant.
© 2015 American Heart Association, Inc.
Fish oil intake reduces serum triglycerides; however, little is known about the effects of dietary fish intake on lipoprotein subclasses.
We aimed at assessing the effect of fatty and lean fish intake on the lipoprotein subclasses in an intervention study.
The intervention study included 33 patients with coronary heart disease, who were aged 61.0 ± 5.8 (mean ± SD) years. The subjects were randomly assigned to a fatty fish (n = 11), lean fish (n = 12), or control (n = 10) diet for 8 weeks. Fish diets included at least 4 fish meals per week. Subjects in the control group consumed lean beef, pork, and chicken. Lipoprotein subclasses and their lipid components were determined by nuclear magnetic resonance spectroscopy.
Concentrations of n-3 fatty acids and docosahexaenoic acid increased in the fatty fish group. The concentrations of cholesterol, cholesterol esters, and total lipids in very large high-density lipoproteins (HDLs) increased in the fatty fish group (overall difference P = .005, P = .002, and P = .007, respectively; false discovery rate P = .04, P = .04, and P = .05, respectively). The mean size of HDL particles increased in the fatty fish group (9.8 ± 0.3 nm at baseline and 9.9 ± 0.4 nm at end of study; overall difference P = .004, false discovery rate P = .04). The fish diets did not affect very-low-density lipoprotein or low-density lipoprotein size.
Fatty fish intake at least 4 times per week increases HDL particle size which might have beneficial effect in patients with coronary heart disease.
A high-throughput proton (1H) nuclear magnetic resonance (NMR) metabonomics approach is introduced to characterise systemic metabolic phenotypes. The methodology combines two molecular windows that contain the majority of the metabolic information available by 1H NMR from native serum, e.g. serum lipids, lipoprotein subclasses as well as various low-molecular-weight metabolites. The experimentation is robotics-controlled and fully automated with a capacity of about 150-180 samples in 24 h. To the best of our knowledge, the presented set-up is unique in the sense of experimental high-throughput, cost-effectiveness, and automated multi-metabolic data analyses. As an example, we demonstrate that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome (n = 4407). The high-throughput of up to 50,000 serum samples per year is also paving the way for this technology in large-scale clinical and epidemiological studies. In contradiction to single 'biomarkers', the application of this holistic NMR approach and the integrated computational methods provides a data-driven systems biology approach to biomedical research.
Although type 2 diabetes is determined primarily by lifestyle and genes, dietary composition may affect both its development and complications. Dietary fat is of particular interest because fatty acids influence glucose metabolism by altering cell membrane function, enzyme activity, insulin signaling, and gene expression. This paper focuses on the prevention of type 2 diabetes and summarizes the epidemiologic literature on associations between types of dietary fat and diabetes risk. It also summarizes controlled feeding studies on the effects of dietary fats on metabolic mediators, such as insulin resistance. Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity. On the other hand, long-chain n-3 fatty acids do not appear to improve insulin sensitivity or glucose metabolism. In dietary practice, foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized. Additional controlled, long-term studies are needed to improve our knowledge on the optimal proportion of different types of fats to prevent diabetes.
Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease (CHD) risk.
The aim of this pilot study was to examine the effects of fatty fish and lean (white) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition.
The study was an 8-week controlled, parallel intervention. Inclusion criteria were myocardial infarction or unstable ischemic attack, age under 70 years, use of betablockers and presence of sinus rhythm. The subjects were randomized to one of the following groups: 4 meals/week fatty fish (n = 11), 4 meals/week lean fish (n = 12) and control diet including lean meat (n = 10).
The mean (+/-SD) of reported fish meals per week was 4.3 +/- 0.4, 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups, respectively. The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only (P < 0.05). Systolic and diastolic blood pressure levels decreased in the lean fish group (0 vs. 8 week: 3.5 +/- 3.2 and 4.6 +/- 3.6%, respectively, P < 0.05). Serum total triglyceride concentration did not significantly change. HDL cholesterol concentration change differed among groups but without significant post hoc differences. Apolipoprotein A-1 concentration decreased in the control group (0 vs. 8 week, P < 0.05). Coagulation factors, 25-hydroxy vitamin D, and heart rate variability (24 h Holter) did not change among the groups.
Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients.
This study was designed to determine whether modifications induced by dietary fats on the high-density lipoprotein3 (HDL3) physicochemical characteristics could affect cholesterol efflux and intracellular cholesterol content, leading to upregulation of low-density lipoprotein (LDL) receptor activity from cultured fibroblasts. Serum HDL3S were obtained from 12 healthy women aged 26 to 49 years who adhered to four 7-week isocaloric diets containing 30% of the caloric intake as fat. Of the total calories, 15.6% of each diet was provided by (1) milk fats, rich in saturated fatty acids; (2) sunflower oil, rich in n-6 polyunsaturated fatty acids; (3) olive oil, rich in monounsaturated fatty acids; and (4) rapeseed oil, rich in n-3 polyunsaturated fatty acids. HDL3 isolated after the monounsaturated fatty acid diet induced the greatest cellular [3H]free cholesterol efflux, reduced the content of intracellular cholesterol, and enhanced 125I-LDL degradation. Univariate regression analyses suggested that the increased capacity of HDL3 to promote cellular [3H]free cholesterol efflux was in part due to its greater fluidity, higher cholesteryl ester content, elevated linoleic to linolenic acid ratio in phospholipids, and its smaller size. In conclusion dietary fats induced physicochemical changes in HDL3, which strongly modulated cellular cholesterol homeostasis in vitro. These data also suggest a novel mechanism by which dietary fats exert their effect on atherosclerosis.
Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?
Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity
- J C Lima-Junior
- De
- Vwm Virginio
- F A Moura
- A Bertolami
- M Bertolami
- O R Coelho-Filho
Lima-Junior JC de, Virginio VWM, Moura FA, Bertolami A,
Bertolami M, Coelho-Filho OR, et al. Excess weight mediates
changes in HDL pool that reduce cholesterol efflux capacity
and increase antioxidant activity. Nutr Metabol Cardiovasc Dis
2020;30:254e64.
https://doi.org/10.1016/j.numecd.2019.09.